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[DOI] [PMC free article] [PubMed] [Google Scholar] Xu G, Kaneto H, Laybutt DR, Duvivier-Kali VF, Trivedi N, Suzuma K, King GL, Weir GC, Bonner-Weir S

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These variations significantly influence the role of GLP-1 in regulating islet function and glucose homeostasis.131 Research indicates that the expression level of GLP-1R on -cells is relatively low.131 Although GLP-1Rs are present, they are limited in number, making the direct inhibitory effect of GLP-1 on -cells relatively weak.247 The primary action often occurs through indirect mechanisms, such as insulin and somatostatin.244 Conversely, the expression level of GLP-1R on -cells is relatively high.248 GLP-1 can effectively bind to receptors on -cells, stimulating the secretion of somatostatin.248 As a broad-spectrum inhibitory hormone, somatostatin can effectively inhibit glucagon secretion from -cells and insulin secretion from -cells.249,250 Relevant studies suggest that the expression of GLP-1R on -cells is crucial for GLP-1s regulation of somatostatin secretion and the overall inhibitory effect on glucagon.248,251,252 This mechanism is particularly evident in the use of GLP-1-based drugs, such as GLP-1RAs, in the treatment of T2DM